It is common in mass spectrometry to use at least two mass spectrometers in series separated by a collision cell. In a triple quadrupole system the first mass spectrometer is a quadrupole operated in a mass resolving mode; the collision cell contains a quadrupole operated in the total ion mode, and the second mass spectrometer is a quadrupole operated in a mass resolving mode. These are commonly referred to as Q1, Q2 and Q3 respectively, and the process is often called MS/MS. In this process, ions are directed into the first mass spectrometer Q1, which selects a parent ion or ions of interest (i.e. a parent ion or ions having a given mass to charge (m/z) ratio). The selected parent ions are then directed into the collision cell Q2, which is commonly pressurized with gas. In the collision cell Q2 the parent ions are fragmented by collision induced dissociation, to produce a number of daughter ions. Alternatively, the parent ions may undergo reactions in the collision gas to form adducts or other reaction products. The term "daughter ion" is intended to mean any of the ion products of the collisions between the parent ions and the gas molecules in the collision cell.
The daughter ions (and remaining parent ions) from the collision cell Q2 then travel into the second mass spectrometer Q3, which is scanned to produce a mass spectrum, usually of the daughter ions.
As is well known, in scanning the second mass spectrometer Q3, the process is as follows Q3 is first set to allow ions in a particular m/z range to pass therethrough by adjusting the magnitude and ratio of the RF to DC voltages applied to the rods of Q3. (RF means radio frequency AC.) After a short time (e.g. 5 milliseconds), called the dwell time, the magnitude of these voltages is changed to a new setting which allows ions in a different (normally higher) m/z range to pass through Q3. Typically ten such settings may be used per atomic mass unit (amu). Thus, for example, the scan may take 50 milliseconds per amu or 50 seconds for a mass spectrum spanning 1,000 amu.
As is also well known, the resolution during the scan can be adjusted by setting the point at which the third mass spectrometer Q3 operates on its characteristic stability diagram (by setting the ratio of the RF and DC voltages on its rods). With a lower DC to RF ratio, the m/z range allowed to pass through Q3 at each setting is larger, resulting in a greater detected signal (i.e. higher sensitivity). However the resolution is usually lower, i.e. it may not be possible to distinguish between ions of closely adjacent mass to charge ratio. Conversely, if Q3 is set for a higher DC to RF ratio, meaning that only ions in a smaller m/z range can pass through Q3 at each setting, then while the resolution may be better, the detected signal or sensitivity is reduced. The smaller detected signal can be a serious problem.
A further problem in triple quadrupole MS/MS is that it is very difficult except under the most favourable conditions to distinguish in quadrupole Q3 between daughter ions whose m/z differs by only one m/z unit. In addition, so far as is known, it has not been possible to distinguish in quadrupole Q3 between daughter ions whose m/z differ by less than one m/z unit. The lack of adequate resolution has long been a problem, since it creates difficulty in interpreting the mass spectra. The difficulty increases when some of the ions are multiply charged, as is common for ions from organic molecules such as peptides and proteins.